Recent studies suggest important roles of glial cells (astrocytes and microglial cells) in the development, differentiation and survival of neurons in the brain. Nerve growth factors secreted from astrocytes are essential for the development and survival of neurons, whereas neurotoxins release from microglial cells (the main immune cells in the brain) in response to adverse neuroimmune reactions may cause the death of neurons and is believed to be the major cause of Neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Earlier studies from our laboratory and others showed the potent effects of opiates on immune cell (T and B cells) functions. Thus, the major purpose of this project is to examine the roles of opioid peptides on neuroimmune functions in the brain. The most exciting finding from this series was the potent inhibition by DYN of the LPS-induced effects. Ultralow concentrations of DYN are within the range of concentrations in the brain, this finding suggests that DYN is an endogenous immune modulator in the brain. Furthermore, fenomolar concentrations of DYN are well below the dissociation constant (kd) values for most of the known opiate receptors (kd around 10-9M), suggesting that a novel non-opiate receptor mediates this inhibitory action of DYN. Thus, characterization and cloning of this non-opiate receptor from microglial cells should reveal an entirely new class of signal transduction systems regulating neuroimmune functions in the brain.